Preliminary study of brca1 and brca2 mutations among vietnamese ovarian carcinomas population by using ion personal genome machine platforms

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Tác giả: Thị Hồng Nhu Bùi, Anh Vũ Hoàng, Thành Chí Hoàng, Quang Thanh Lê, Thái Khương Lê, Đại Phú Ngô, Vĩnh Tường Ngô, Đăng Quân Nguyễn, Duy Sinh Nguyễn, Trọng Bình Nguyễn, Huy Hoà Phạm, Thanh Nhân Võ

Ngôn ngữ: vie

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Thông tin xuất bản: Tạp chí khoa học đại học huế: khoa học tự nhiên, 2020

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ID: 489151

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BRCA1 and BRCA2 are two important tumor suppressor genes. The germline and somatic mutations of these two genes in ovarian carcinomas are sensitive for treatment with ADP-ribose polymerase enzyme inhibitor (PARPi). Recently, several PARPi drugs, such as Olaparib and Rucaparib, have been approved for ovarian cancer with BRCA1/2 germline mutations by Food and Drug Administration (FDA), and for both germline and somatic mutations by European Medicines Agency (EMA). However, there have no been reliable data about the prevalence of mutations of these two genes in ovarian carcinomas population for treatment in Vietnam so far. Therefore, we studied the prevalence of the BRCA1/2 germline and somatic mutations among ovarian carcinomas patients in the Vietnamese population. In this study, we sequenced these two genes by using Ion Torrent PGM. The subjects of the study are 11 formalin-fixed paraffin-embedded tumor (FFPE) samples from 11 patients with ovarian carcinomas obtained from Tu Du Hospital of Obstetrics and Gynecology (Vietnam). Multiplex PCR then was performed on the DNA samples and two controls containing known mutations by using Oncomine BRCA Research Assay. Of the sequenced 11 samples, a pathogenic mutation (1/11 patient, 9.1%) detected on the BRCA1 gene was a nonsense point mutation causing stop codon at the position of amino acid 1772. Consequently, our sequencing workflow shows the success in identifying and investigating the prevalence of BRCA1/2 mutation in a small group of ovarian carcinomas with FFPE tumor samplesBRCA1 và BRCA2 là hai gen ức chế khối u quan trọng. Việc đột biến hai gen này ở bệnh nhân ung thư biểu mô buồng trứng dòng mầm và dòng sinh dưỡng thì đáp ứng tốt hơn với thuốc ức chế enzyme poly(ADP-ribose) polymerase inhibitor (PARPi). Gần đây, một vài thuốc PARPi, như Olaparib và Rucaparib, đã được chấp thuận dùng cho bệnh nhân ung thư buồng trứng với đột biến dòng mầm BRCA1/2 bởi Food and Drug Administration (FDA) và với đột biến dòng mầm và dòng sinh dưỡng đối với European Medicines Agency (EMA). Tuy nhiên, hiện nay Việt Nam chưa có dữ liệu nào đáng tin cậy về tình trạng đột biến hai gen này trong quần thể bệnh nhân ung thư biểu mô buồng trứng nhằm hỗ trợ cho điều trị. Do đó, chúng tôi tiến hành giải trình tự nhằm khảo sát đột biến hai gen BRCA1/2 dòng mầm và dòng sinh dưỡng ở bệnh nhân ung thư biểu mô buồng trứng người Việt Nam. Trong nghiên cứu này, chúng tôi tiến hành giải trình tự hai gen này bằng Ion Torrent PGM. Đối tượng nghiên cứu là 11 mẫu mô vùi nến được thu nhận từ Bệnh viện Từ Dũ của 11 bệnh nhân ung thư biểu mô buồng trứng. DNA từ các mẫu này và 2 mẫu đối chứng đã biết thông tin đột biến được tiến hành multilplex PCR với kit Oncomine BRCA Research Assay. Trong mười một mẫu được giải trình tự, một đột biến gây bệnh (1/11 bệnh nhân
9,1%) đã được phát hiện trên gen BRCA1, là đột biến điểm đưa codon stop vào trình tự protein tại vị trí axit amin 1772. Tóm lại, quy trình giải trình tự của chúng tôi thành công trong việc xác định và khảo sát tỉ lệ đột biến BRCA1/2 trong một nhóm nhỏ bệnh nhân ung thư biểu mô buồng trứng với mẫu sinh phẩm là mô vùi nến.

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